Is PEX1 p.Arg798Gly (c.2392C>G) pathogenic?

PEX1 p.Arg798Gly (c.2392C>G) is classified Likely pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). AlphaMissense: likely benign (0.0862); Very rare (popmax 0.000678%, nfe); Associated with Heimler syndrome 1.

What condition is associated with PEX1 p.Arg798Gly (c.2392C>G)?

PEX1 p.Arg798Gly (c.2392C>G) is associated with Heimler syndrome 1 (ClinVar).

How common is PEX1 p.Arg798Gly (c.2392C>G) in the general population?

PEX1 p.Arg798Gly (c.2392C>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about PEX1 p.Arg798Gly (c.2392C>G)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

PEX1 p.Arg798Gly

c.2392C>G · rs61750419 · VCV2677620

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Heimler syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign ⚠ discordant with ClinVar
REVEL	0.603	indeterminate
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP 0.76
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	12.97	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,730 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,620 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PEX1
Protein: p.Arg798Gly
Coding: c.2392C>G
MANE Select: NM_000466
dbSNP: rs61750419
Type: single nucleotide variant
Location: chr7:92501914 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 798: a UniProt-annotated variant site (in pbd1a); a UniProt-annotated variant site (in pbd-cg1)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Heimler syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX1 p.Arg798Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
PEX1 p.Arg798His Uncertain significance ★ ⚠ same residue
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1587+1G>A Likely pathogenic ★★ same condition
PEX1 c.1670+1G>T Pathogenic ★★ same condition
PEX1 c.2784-1G>C Likely pathogenic ★★ same condition
PEX1 c.2927-2A>G Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pex1-p-arg798gly (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown